The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin-1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary-albumin-to-creatinine-ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = −0.64, P = 0.046, median change UACR: −40.1%, 95% confidence interval (CI): −22.9 to −77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin-1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [11C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC0–last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.
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Purpose of this longitudinal observational study was to (i) examine the change of daily physical activity in 28 adult kidney transplant recipients over the first 12 months following transplantation; and (ii) to examine the change in metabolic characteristics and renal function. Accelerometer-based daily physical activity and metabolic- and clinical characteristics were measured at six wk (T1), three months (T2), six months (T3) and 12 months (T4) following transplantation. Linear mixed effect analyses showed an increase in steps/d (T1 = 6326 ± 2906; T4 = 7562 ± 3785; F = 3.52; p = 0.02), but one yr after transplantation only 25% achieved the recommended 10 000 steps/d. There was no significant increase in minutes per day spent on moderate-to-vigorous intensity physical activity (T1 = 80.4 ± 63.6; T4 = 93.2 ± 55.1; F = 1.71; p = 0.17). Body mass index increased over time (T1 = 25.4 ± 3.2; T4 = 27.2 ± 3.8; F = 12.62; p < 0.001), mainly due to an increase in fat percentage (T1 = 30.3 ± 8.0; T4 = 34.0 ± 7.9; F = 14.63; p < 0.001). There was no significant change in renal function (F = 0.17; p = 0.92). Although the recipients increased physical activity, the majority did not meet the recommended levels of physical activity after one yr. In addition to the weight gain, this may result in negative health consequences. Therefore, it is important to develop strategies to support kidney transplant recipients to comply with healthy lifestyle recommendations, including regular physical activity.
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BACKGROUND: Acute kidney injury (AKI) often occurs in critically ill patients. AKI is associated with mortality and morbidity. Interventions focusing on the reduction of AKI are suggested by the Kidney Disease: Improving Global Outcomes guideline. We hypothesized that these educational interventions would improve outcome in patients admitted to the Intensive Care Unit (ICU).METHODS: This was a pragmatic single-centre prospective observational before-after study design in an ICU in a tertiary referral hospital. All consecutive patients admitted to the ICU irrespective their illness were included. A 'Save the Kidney' (STK) bundle was encouraged via an educational intervention targeting health care providers. The educational STK bundle consisted of optimizing the fluid balance (based on urine output, serum lactate levels and/or central venous oxygen saturation), discontinuation of diuretics, maintaining a mean arterial pressure of at least 65 mmHg with the potential use of vasopressors and critical evaluation of the indication and dose of nephrotoxic drugs. The primary outcome was the composite of mortality, renal replacement therapy (RRT), and progression of AKI. Secondary outcomes were the components of the composite outcome the severity of AKI, ICU length of stay and in-hospital mortality.MAIN RESULTS: The primary outcome occurred in 451 patients (33%) in the STK group versus 375 patients (29%) in the usual care group, relative risk (RR) 1.16, 95% confidence interval (CI) 1.03-1.3, p < 0.001. Secondary outcomes were, ICU mortality in 6.8% versus 5.6%, (RR 1.22, 95% CI 0.90-1.64, p = 0.068), RRT in 1.6% versus 3.6% (RR 0.46, 95% CI 0.28-0.76, p = 0.002), and AKI progression in 28% versus 24% (RR 1.18, 95% CI 1.04-1.35, p = 0.001).CONCLUSIONS: Providing education to uniformly apply an AKI care bundle, without measurement of the implementation in a non-selected ICU population, targeted at prevention of AKI progression was not beneficial.
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